Exploring the mechanism of Licorice in the treatment of liver injury induced by Semen Strychni based on network pharmacology,molecu-lar docking and animal experiments
10.12092/j.issn.1009-2501.2025.10.005
- VernacularTitle:基于网络药理学、分子对接和动物实验探讨甘草缓解马钱子肝损伤的作用机制
- Author:
Xiaoyan FU
1
;
Zihan GONG
;
Guangmiao GAO
;
Biqian YANG
;
Yi DENG
;
Liping WANG
;
Xiujuan YANG
;
Zhijun YANG
Author Information
1. 甘肃中医药大学,兰州 730000,甘肃
- Publication Type:Journal Article
- Keywords:
licorice;
Semen Strychni;
network pharmacology;
molecular docking;
DILI;
PI3K-AKT signaling pathway
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2025;30(10):1326-1341
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the potential mechanism of licorice on liver injury induced by Se-men Strychni based on network pharmacology,mo-lecular docking combined with animal experiments,providing an effective strategy for prevention and treatment of liver injury induced by Semen Strych-ni.METHODS:Firstly,the active ingredients of Se-men Strychni and licorice were obtained through the ETCM,TCMSP database and analysis platform,CTD database and literature supplementation.Then,the potential toxic ingredients of Semen Strychni were further screened based on the Swis-sADME platform,and the targets corresponding to the active ingredients were predicted through the SwissTargetPrediction platform.By using the Gene-Cards and OMIM databases to collect DILI-related targets,the potential targets for licorice to alleviate liver injury caused by Semen Strychni were ob-tained.By constructing the active ingredient-target network,the core ingredients of licorice in alleviat-ing liver injury caused by Semen Strychni were screened.The key targets obtained were used to construct and analyze the protein-protein interac-tion networks(PPI)through the STRING database and Cytoscape 3.9.0 software.The potential targets were subjected to GO and KEGG pathway enrich-ment analysis with the aid of the DAVID database,and constructed a network of active ingredient-tar-get-pathway.Molecular docking study was ap-proved for the core targets and the active ingredi-ents by using Schrodinger 2023-1 software,and the visualization operation was conducted through Py-mol.Finally,the regulatory effect of licorice on the key pathway of liver injury caused by Semen Strych-ni was validated by establishing a rat model of liver injury induced by Semen Strychni.RESULTS:After screening,6 potential toxic components of Semen Strychni and 104 corresponding targets,89 active components of licorice and 347 corresponding tar-gets,and 3 200 DILI targets were obtained.A total of 23 intersection targets were obtained through Venn analysis.By constructing the active ingredi-ent-target network,it was found that the main core ingredients were 7-methoxy-2-methyl isofla-vone,medicarpin,shinpterocarpin,quercetin,for-mononetin and isoliquiritigenin.The PPI network indicated that the core targets were protein kinase B1(AKT1),epidermal growth factor receptor(EG-FR),human epidermal growth factor receptor 2(ERBB2),glycogen synthase kinase 3 beta(GSK3B),kinase insert domain receptor(KDR)and Janus ki-nase 2(JAK2).A total of 39 relevant pathways were enriched in KEGG(P＜0.01),among which the phos-phatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)(PI3K-AKT)signaling pathway,which has been confirmed and ranks first in enrichment,and was closely related to liver injury.Molecular docking re-sults showed that the core components have good binding ability with the core targets.In vivo animal experiments demonstrated that,compared to the model group,licorice significantly reduced the liver index(P＜0.01),serum levels of alkaline phospha-tase(ALP),alanine aminotransferase(ALT),aspar-tate aminotransferase(AST),indirect bilirubin(IBIL),and total bilirubin(TBIL)in rats with liver in-jury,while increasing total protein(TP)levels(P＜0.05 or P＜0.01).Additionally,licorice alleviated con-gestion in the central veins and hepatic sinusoids,improved the alignment of hepatocytes,and re-duced inflammatory cell infiltration.Furthermore,licorice significantly decreased the levels of malo-ndialdehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)in the liver tissue of injured rats,while elevating the levels of superoxide dismutase(SOD)and glutathi-one peroxidase(GSH-Px)(P＜0.01).It also markedly downregulated the phosphorylation levels of PI3K and AKT(P＜0.01).CONCLUSION:Licorice has multi-component and multi-target properties in the treat-ment of liver injury induced by Semen Strychni,which may play a hepatoprotective role by inhibit-ing the activation of PI3K-AKT signaling pathway.
